Department of Ophthalmology, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, China.
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2189-2195. doi: 10.26355/eurrev_202003_20484.
To explore the relationship between micro ribonucleic acid (miR)-375 in regulating the N-Myc downstream-regulated gene 2 (Ndrg2)/interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and diabetic retinopathy (DR) in rats.
Thirty Sprague- Dawley rats were randomly divided into Control group (n=10), Model group (n=10), and miR-375 inhibitor group [miR-375 small interfering RNA (siRNA) group, n=10]. The rats in Model group were injected with streptozotocin (STZ) via the tail vein to prepare into rat models of diabetes. The body weight, fasting blood glucose, and retinal barrier permeability of rats in each group were detected. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in rat serum were measured using kits. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay was performed to determine the apoptosis of optic ganglion cells in rat retinal tissues. Additionally, the messenger RNA (mRNA) and protein levels of Ndrg2, IL-6 and STAT3 in rat retinal tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively.
Compared with Control group, Model group had reduced body weight of rats, increased blood glucose and retinal permeability of rats, raised serum MDA content, decreased SOD activity, up-regulated apoptotic rate of optic ganglia, and notably elevated mRNA and protein levels of Ndrg2, IL-6 and STAT3 in retinal tissues. Compared with those in Model group, the body weight of rats declined, the blood glucose of rats rose, the retinal permeability of rats was decreased significantly, the serum MDA content was reduced, the SOD activity was raised, the apoptotic rate of optic ganglia was decreased, and the mRNA and protein levels of Ndrg2, IL-6 and STAT3 in retinal tissues were also decreased significantly in miR-375 siRNA group.
MiR-375 inhibitors are able to reduce blood glucose, retinal permeability, and optic ganglion apoptosis in rats with DR, and the mechanism of action may be related to the regulation on the Ndrg2/IL-6/STAT3 signaling pathway.
探讨微小 RNA（miR）-375 调控 N-肌醇依赖性蛋白激酶 2（Ndrg2）/白细胞介素 6（IL-6）/信号转导子和转录激活子 3（STAT3）信号通路与糖尿病视网膜病变（DR）的关系。
30 只 Sprague-Dawley 大鼠随机分为对照组（n=10）、模型组（n=10）和 miR-375 抑制剂组[miR-375 小干扰 RNA（siRNA）组，n=10]。模型组大鼠经尾静脉注射链脲佐菌素（STZ）制备糖尿病大鼠模型。检测各组大鼠的体重、空腹血糖和视网膜屏障通透性。试剂盒检测大鼠血清丙二醛（MDA）和超氧化物歧化酶（SOD）水平。末端脱氧核苷酸转移酶介导的脱氧尿嘧啶三磷酸生物素缺口末端标记（TUNEL）法检测大鼠视网膜神经节细胞凋亡。逆转录-聚合酶链反应（RT-PCR）和 Western blot 分别检测大鼠视网膜组织中 Ndrg2、IL-6 和 STAT3 的信使 RNA（mRNA）和蛋白水平。
与对照组比较，模型组大鼠体重降低，血糖和视网膜通透性升高，血清 MDA 含量升高，SOD 活性降低，神经节细胞凋亡率升高，视网膜组织中 Ndrg2、IL-6 和 STAT3 的 mRNA 和蛋白表达水平均升高。与模型组比较，miR-375 siRNA 组大鼠体重降低，血糖升高，视网膜通透性明显降低，血清 MDA 含量降低，SOD 活性升高，神经节细胞凋亡率降低，视网膜组织中 Ndrg2、IL-6 和 STAT3 的 mRNA 和蛋白表达水平均降低。
miR-375 抑制剂可降低 DR 大鼠血糖、视网膜通透性和神经节细胞凋亡，其作用机制可能与调控 Ndrg2/IL-6/STAT3 信号通路有关。
